March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Suppression Of Corneal Lymphangiogenesis And Rejection Reaction After Corneal Transplantation By Using An Anti-podoplanin Antibody
Author Affiliations & Notes
  • Yuko Maruyama
    Ophthalmology, Kyoto prefectural University of Medicine, Kyoto, Japan
  • Kazuichi Maruyama
    Ophthalmology, Kyoto prefectural University of Medicine, Kyoto, Japan
  • Yukinari Kato
    Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology, Yamagata University Faculty of Medicine, Yamagata, Japan
  • Shigeru Kinoshita
    Ophthalmology, Kyoto prefectural University of Medicine, Kyoto, Japan
  • Footnotes
    Commercial Relationships  Yuko Maruyama, None; Kazuichi Maruyama, None; Yukinari Kato, None; Shigeru Kinoshita, None
  • Footnotes
    Support  KAKEN23592613
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2389. doi:
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      Yuko Maruyama, Kazuichi Maruyama, Yukinari Kato, Shigeru Kinoshita; Suppression Of Corneal Lymphangiogenesis And Rejection Reaction After Corneal Transplantation By Using An Anti-podoplanin Antibody. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2389.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Podoplanin has been shown to be a reliable marker of lymphatic endothelium, but its role in the lymphatic system has yet to be well-investigated. The purpose of this present study was to investigate the role of podoplanin in lymphangiogenesis and macrophage inflammation by blocking podoplanin (PMab-1) using a mouse corneal inflammation model.

Methods: : Three 11-0 nylon sutures were placed intrastromally in BALB/c mice. PMab-1 (100 µg) was then injected into a tail vein of each mouse at 0, 1, 2, 3, and 5 days after suture placement. Lymphatic vessels were visualized at postoperative day 7 when the corneas of each mouse were collected and stained with anti-LYVE-1. The area covered by LYVE-1+ vessels was determined using National Institutes of Health imaging software. For a corneal transplantation model, C57BL/6 mice were used as donors and BALB/c mice were used as hosts. PMab-1 (150 µg) or rabbit IgG was injected into the subconjunctival space of each host mouse at 0, 3, 5, and 7 days after corneal transplantation. The status of the corneal transplant was then assessed at postoperative day 56. Macrophages were collected from the peritoneal cavity of the male C57BL/6 mice, then cultured and stimulated with 1ng/ml lipopolysaccharides (LPS), at 1, 10, 100µg/ml of PMab-1, respectively. TNF-α in culture medium was measured by ELISA.

Results: : Administration of PMab-1 reduced lymphangiogenesis in the corneas in the suture placement model mice (P<0.05) and led to a significant suppression of the rejection reaction in the corneal transplantation model mice (85% vs control 40% survival rate; p=0.0259). The production of TNF-α induced by LPS was significantly suppressed with all concentrations of PMab-1 (p<0.03).

Conclusions: : The findings of this study show that blocking podoplanin inhibits lymphatic growth associated with corneal wound healing and also inhibits macrophage inflammation. These data suggest that podoplanin is a novel therapeutic target for inflammation.

Keywords: neovascularization • transplantation 
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